Selective increases in the cytokine, TNF, in the prefrontal cortex of PCP-treated rats and human schizophrenic subjects: influence of antipsychotic drugs

¹ Yoshitomi Research Institute of Neuroscience in Glasgow, University of Glasgow, Glasgow, UK.
² Department of Biomedical Science, University of Sheffield, Sheffield, UK.
³ Yoshitomi Research Institute of Neuroscience in Glasgow, University of Glasgow, Glasgow, UK. Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, UK.
⁴ Yoshitomi Research Institute of Neuroscience in Glasgow, University of Glasgow, Glasgow, UK. Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK.

^* To whom correspondence should be addressed.

	Abstract

The psychotomimetic drug phencyclidine (PCP) induces symptoms closely related to those of schizophrenia in humans. In order to test the hypothesis that cytokines may be involved in the aetiology and treatment of schizophrenia, this study investigated the levels of cytokine mRNAs in rat brain after acute and chronic administration of PCP, in the presence and absence of antipsychotic drugs. The levels of the mRNAs encoding TNF, IL-2, IL-6, TGF1, 2, 3, IL-3 and GM-CSF were measured in the prefrontal cortex, cortex, hippocampus, ventral and dorsal striatum regions of male hooded Long Evans rats after acute drug administration. Antipsychotic drugs and PCP significantly reduced the levels of TNF in the prefrontal cortex compared to vehicle-treated animals, whilst other cytokines remained unchanged. In addition, significant reductions in the levels of TNF mRNA in the prefrontal cortex still occurred 24 h after acute PCP administration. However, levels of TNF mRNA were restored to control values after chronic PCP treatment, whereas increased expression was detected in animals co-administered with haloperidol. Levels of TNF mRNA were also found to be significantly increased in the prefrontal cortex of schizophrenic subjects. The relationship between TNF levels and schizophrenia are discussed.

Key Words: TNF, psychosis, prefrontal cortex, cytokines, schizophrenia

First published on February 14, 2006, doi:10.1177/0269881106062025

Journal of Psychopharmacology 2006;20:636.

A more recent version of this article appeared on September 1, 2006


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